Serious pulmonary toxicity in patients with Hodgkin's lymphoma with SGN-30, gemcitabine, vinorelbine, and liposomal doxorubicin is associated with an FcγRIIIa-158 V/F polymorphism
Serious pulmonary toxicity in patients with Hodgkin's lymphoma with SGN-30, gemcitabine, vinorelbine, and liposomal doxorubicin is associated with an FcγRIIIa-158 V/F polymorphism
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DOI：
10.1093/annonc/mdq211
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发表时间：
2010-11-01
影响因子：
50.5
通讯作者：
Bartlett, N. L.
中科院分区：
文献类型：
--
作者：
Blum, K. A.;Jung, S. -H;Bartlett, N. L.
背景：基于抗cd30抗体联合吉西他滨的体外协同细胞毒性，癌症和白血病B组在复发霍奇金淋巴瘤患者中进行了一项双盲，随机，SGN-30联合吉西他滨，维诺瑞滨和聚乙二醇脂质体多柔比星（GVD）的II期试验。患者和方法：在试验的第一部分中，16例患者接受SGN-30联合GVD治疗，以评估联合用药的安全性。在第2部分中，患者被随机分配到SGN-30 （n = 7）或安慰剂（n = 7）与GVD，以确定总缓解率（ORR）。结果：所有30例患者的ORR为63% （SGN-30加GVD组65%，n = 23，安慰剂加GVD组57%，n = 7）。中位无事件生存期为9.0个月，两组间无差异。5名接受SGN-30和GVD治疗的患者出现3-5级肺炎，导致试验过早结束。所有5例肺毒性患者Fc γ RIIIa基因均存在V/F多态性（P = 0.008）。结论：结合历史数据显示2%的GVD肺部事件发生率，这些结果表明SGN-30不能安全地同时使用。在Fc γ RIIIa V/F多态性患者中，SGN-30和GVD合并肺炎的风险最大。
Background: Based on in vitro synergistic cytotoxicity when anti-CD30 antibodies are combined with gemcitabine, the Cancer and Leukemia Group B conducted a double-blind, randomized, phase II trial of SGN-30 with gemcitabine, vinorelbine, and pegylated liposomal doxorubicin (GVD) in patients with relapsed Hodgkin's lymphoma.Patients and methods: In part 1 of the trial, 16 patients received SGN-30 with GVD to assess the safety of the combination. In part 2, patients were randomly allocated to SGN-30 (n = 7) or placebo (n = 7) with GVD to determine overall response rate (ORR).Results: ORR in all 30 patients was 63% (65% with SGN-30 plus GVD, n = 23, and 57% with placebo plus GVD, n = 7). Median event-free survival was 9.0 months, with no difference between the two arms. Grades 3-5 pneumonitis occurred in five patients receiving SGN-30 and GVD, leading to premature closure of the trial. All five patients with pulmonary toxicity had a V/F polymorphism in the Fc gamma RIIIa gene (P = 0.008).Conclusions: Together with historical data demonstrating a 2% incidence of pulmonary events with GVD, these results indicate that SGN-30 cannot safely be administered concurrently. The risk of pneumonitis with SGN-30 and GVD is greatest in patients with an Fc gamma RIIIa V/F polymorphism.